This invention relates to novel N-(acyl)-p-amino-N'-(mono-substituted) benzamides and to their use as anti-ulcer agents.
Chronic gastric and duodenal ulcers, collectively known as peptic ulcers, are a common ailment for which a variety of treatments have been developed. The treatment depends upon the severity of the ulcer and ranges in scope from simple dietary measures to medicinal or drug treatment and surgery.
Peptic ulcer management by drug therapy has received significant attention recently and most of the drugs which have been developed avoid the anti-cholinergic approach inherent in atropine derivatives because of that approach's undesirable side effects such as tachycardia, dry mouth and diarrhea. ("The Pharmacological Basis of Therapeutics," L. S. Goodman and A. Gilman, Eds. Macmillan, New York 1970). Some examples of these recently developed drugs are glycyrrhetinic acid derivatives (U.S. Pat. No. 3,891,750) and antisecretory compounds such as phenoxy pyrimidines (U.S. Pat. No. 3,862,190).
One of the most widely acclaimed anti-ulcer agents used for treatment is the glycyrrhetinic acid derivative, carbenoxolone sodium ("Carbenoxolone Sodium: a symposium," J. M. Robinson and F. M. Sullivan, Eds., Butterworth, London, 1968). It has been reported to prevent formation and to promote healing of gastric ulcers in animal models and has been shown to promote healing in controlled clinical trials. Carbenoxolone sodium has been prescribed for ulcer sufferers by European general practitioners and is a derivative of the essence of the European folk remedy (licorice) for ulcers. It is, however, not without its untoward side effects, which result from its similarity in pharmacology and structural features to adrenocorticosteroids (J. Groen, et al., Acta, Med. Scand. Suppl., 312, 745 (1956)). These aldosterone-like properties include such effects as anti-diuresis, potassium loss and muscle wasting, and obviously detract from carbenoxolone's benefaction.
From a search to find anti-ulcer compounds having selective carbenoxolone characteristics, it has been surprisingly discovered that N-(acyl)-p-amino-N'-(monosubstituted) benzamides have carbenoxolone-like anti-ulcer activity in animal models.